Memory dysfunction associated with aging, neurodegenerative and psychiatric disorders represents an increasing medical need. Advances in research exploring the biological mechanisms underlying learning and memory have opened new potential approaches for development of memory-enhancing therapies addressed to selective neuronal targets. In this work, we synthesized some derivatives with a pyrazolo[ 5,1-c][1,2,4]benzotriazine core to identify ligands on GABAA receptors subtype (benzodiazepine site on GABAA-receptor) endowed with the potential of enhancing cognition activity without the side effects usually associated with non-selective GABAA modulators. In fact, there is much evidence that GABAA-R (c-aminobutyric acid, type A receptor) subtype ligands have relevance in learning and memory. In vitro and in vivo tests have been performed. Pharmacological data indicate that compounds 7, 13, 14 and 22 act as dual functional modulators of GABAA-Rs (promnemonic and anxiolytic agents) while only compounds 3 and 10 stand out as selectively displaying good antiamnesic and procognitive activity (1 and 3 mg/kg, respectively).

Synthesis of novel cognition enhancer with pyrazolo[5,1-c][1,2,4]benzotriazine core acting at gamma-aminobutyric acid type A (GABAA) receptor / Gabriella Guerrini; Giovanna Ciciani; Annarella Costanzo; Simona Daniele; Caludia Martini; Carla Ghelardini; Lorenzo Di Cesare Mannelli.. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 1464-3391. - ELETTRONICO. - 21:(2013), pp. 2186-2198. [10.1016/j.bmc.2013.02.027]

Synthesis of novel cognition enhancer with pyrazolo[5,1-c][1,2,4]benzotriazine core acting at gamma-aminobutyric acid type A (GABAA) receptor.

GUERRINI, GABRIELLA;CICIANI, GIOVANNA;COSTANZO, ANNARELLA;GHELARDINI, CARLA;DI CESARE MANNELLI, LORENZO
2013

Abstract

Memory dysfunction associated with aging, neurodegenerative and psychiatric disorders represents an increasing medical need. Advances in research exploring the biological mechanisms underlying learning and memory have opened new potential approaches for development of memory-enhancing therapies addressed to selective neuronal targets. In this work, we synthesized some derivatives with a pyrazolo[ 5,1-c][1,2,4]benzotriazine core to identify ligands on GABAA receptors subtype (benzodiazepine site on GABAA-receptor) endowed with the potential of enhancing cognition activity without the side effects usually associated with non-selective GABAA modulators. In fact, there is much evidence that GABAA-R (c-aminobutyric acid, type A receptor) subtype ligands have relevance in learning and memory. In vitro and in vivo tests have been performed. Pharmacological data indicate that compounds 7, 13, 14 and 22 act as dual functional modulators of GABAA-Rs (promnemonic and anxiolytic agents) while only compounds 3 and 10 stand out as selectively displaying good antiamnesic and procognitive activity (1 and 3 mg/kg, respectively).
2013
21
2186
2198
Gabriella Guerrini; Giovanna Ciciani; Annarella Costanzo; Simona Daniele; Caludia Martini; Carla Ghelardini; Lorenzo Di Cesare Mannelli.
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/797485
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